Metformin Restores the Penile Expression of Nitric Oxide Synthase in High-Fat-Fed Obese Rats

• Published in: Journal of andrology Vol. 28; no. 4; pp. 555 - 560
• Main Authors: Kim, Yong-Woon, Park, So-Young, Kim, Jong-Yeon, Huh, Jung-Yoon, Jeon, Woo-Sung, Yoon, Chang-Jun, Yun, Sung-Su, Moon, Ki-Hak
• Format: Journal Article
• Language: English
• Published: Oxford, UK Am Soc Andrology 01.07.2007; Blackwell Publishing Ltd; American Society of Andrology
• Subjects: Adenylate Kinase - blood; Adipose Tissue - anatomy & histology; AMP‐activated protein kinase; Animals; Biological and medical sciences; Body Weight; Dietary Fats; Fundamental and applied biological sciences. Psychology; Gynecology. Andrology. Obstetrics; Male; Male genital diseases; Mammalian male genital system; Medical sciences; Metabolic diseases; Metformin - therapeutic use; Nitric Oxide Synthase - genetics; Nitric Oxide Synthase Type III - genetics; Obesity; Obesity - enzymology; Obesity - etiology; Organ Size; penile tissue; Penis - enzymology; Rats; Rats, Mutant Strains; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; Vertebrates: reproduction; EC 1.14.13.39; Obesity; Rat; Enzyme; Transferases; penile tissue; Rodentia; Nutrition disorder; EC 2.7.1.37; AMP-activated protein kinase; Male genital system; Nitric-oxide synthase; Feeding; Vertebrata; Reproduction; Mammalia; Protein kinase; Penis; Animal; Oxidoreductases; Nutritional status
• ISSN: 0196-3635; 1939-4640
• DOI: 10.2164/jandrol.106.001602

Obesity is a well‐known risk factor for erectile dysfunction, which is associated with reduced penile nitric oxide synthase (NOS) expression. Recently it was reported that metformin activates AMP‐activated protein kinase (AMPK), which increases the expression of neuronal (n) NOS and endothelial (e) NOS. Thus, to evaluate whether metformin restores NOS expression in penile tissue, we measured penile expression of nNOS and eNOS after 4 weeks of metformin treatment (300 mg/kg/d) in 5‐month‐old high‐ fat—fed obese (HFO) rats. HFO rats have increased fat accumulation in visceral areas and marked suppression of nNOS and eNOS expression in penile tissue. However, metformin treatment decreased visceral fat deposition and restored nNOS and eNOS expression in penile tissue. The levels of AMPK and phosphorylated AMPK were also decreased in HFO rats but were subsequently elevated by metformin treatment. These results suggest that expression of NOS was suppressed by the high‐fat diet but restored by metformin treatment. The effect of metformin on the expression of NOS may be associated with its activation of AMPK.